Summaries for Patients|7 March 2006

Adding Chloroquine to Conventional Chemotherapy and Radiotherapy for Glioblastoma Multiforme

The summary below is from the full report titled “Adding Chloroquine to Conventional Treatment for Glioblastoma Multiforme. A Randomized, Double-Blind, Placebo-Controlled Trial.” It is in the 7 March 2006 issue of Annals of Internal Medicine (volume 144, pages 337-343). The authors are J. Sotelo, E. Briceño, and M.A. López-González.

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What is the problem and what is known about it so far?

Glioblastoma multiforme is a type of brain cancer that is difficult to treat. Even with aggressive treatment, including surgery, chemotherapy (cancer-fighting drugs), and radiotherapy (cancer-fighting radiation), most people with this disease only survive about 1 year after diagnosis. Glioblastoma multiforme is difficult to treat because the cancer cells develop genetic mutations that cause them to be resistant to treatment, which means that previously effective treatment no longer fights the cancer cells. Chloroquine is a drug that is most often used to treat malaria, an infection that is spread by mosquitoes in some parts of the world. Researchers have observed that chloroquine can make it more difficult for some cells to develop genetic mutations and have hypothesized that chloroquine might prevent glioblastoma cells from developing the mutations that cause them to become resistant to standard treatment. Early studies done in rats support this hypothesis.

Why did the researchers do this particular study?

Who was studied?

30 patients with glioblastoma multiforme who received care at the National Institute of Neurology and Neurosurgery in Mexico. To be included in the study, patients had to be younger than 60 years of age, have glioblastoma that involved only 1 side of the brain, not have other major illnesses, and be well enough to care for themselves.

How was the study done?

From October 2000 through January 2004, the researchers randomly assigned patients who agreed to be in the study to receive either daily chloroquine, 150 mg, or a placebo pill that contained no active ingredient. The patients received chloroquine or placebo for 12 months beginning 5 days after surgery to remove the cancer. All 30 patients also received standard chemotherapy and radiotherapy. The researchers then followed patients to see who was still alive as of October 2005.

What did the researchers find?

As of October 2005, 6 of the 15 patients in the chloroquine group were alive compared with 3 patients in the placebo group. Surviving patients in the chloroquine group had survived 59, 45, 30, 27, 27, and 20 months after surgery compared with 32, 25, and 22 months for the surviving patients who received placebo. Median survival time was 24 months for patients in the chloroquine group and 11 months for patients in the placebo group. The median is the middle of the distribution, which means that half of the patients survived longer and half died sooner than the reported median survival time.

What were the limitations of the study?

Despite the promising findings, the study was too small to provide a definite answer about whether chloroquine improved survival in patients with glioblastoma multiforme. It was also too small to determine whether chloroquine leads to unwanted side effects.

What are the implications of the study?

This preliminary study suggests that larger, more definitive studies should be done to evaluate whether the addition of chloroquine to conventional treatment improves outcomes for patients with glioblastoma multiforme.

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